PMID- 32685351
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240329
IS  - 2192-8304 (Print)
IS  - 2192-8312 (Electronic)
IS  - 2192-8304 (Linking)
VI  - 54
IP  - 1
DP  - 2020 Jul
TI  - Treatment of infantile neuroaxonal dystrophy with RT001: A di-deuterated ethyl 
      ester of linoleic acid: Report of two cases.
PG  - 54-60
LID - 10.1002/jmd2.12116 [doi]
AB  - BACKGROUND: Infantile neuroaxonal dystrophy (INAD) is a rare, autosomal recessive 
      disease due to defects in PLA2G6 and is associated with lipid peroxidation. RT001 
      is a di-deuterated form of linoleic acid that protects lipids from oxidative 
      damage. METHODS: We evaluated the pharmacokinetics (PK), safety, and 
      effectiveness of RT001 in two subjects with INAD (subject 1: 34 months; subject 
      2: 10 months). After screening and baseline evaluations, subjects received 1.8 g 
      of RT001 BD. PK analysis and clinical evaluations were made periodically. MAIN 
      FINDINGS: Plasma levels of deuterated linoleic acid (D2-LA), deuterated 
      arachidonic acid (D2-AA), D2-LA to total LA, and D2-AA to total AA ratios were 
      measured. The targeted plasma D2-LA ratio (>20%) was achieved by month 1 and 
      maintained throughout the study. RBC AA-ratios were 0.11 and 0.18 at 6 months for 
      subjects 1 and 2; respectively. No treatment-related adverse events occurred. 
      Limited slowing of disease progression and some return of lost developmental 
      milestones were seen. CONCLUSIONS: Oral RT001 was administered safely in two 
      subjects with INAD. Early findings suggest that the compound was well tolerated, 
      metabolized and incorporated in the RBC membrane. A clinical trial is underway to 
      assess efficacy.
CI  - (c) 2020 The Authors. Journal of Inherited Metabolic Disease published by John 
      Wiley & Sons Ltd on behalf of SSIEM.
FAU - Adams, Darius
AU  - Adams D
AD  - Atlantic Health System Goryeb Children's Hospital Morristown New Jersey USA.
FAU - Midei, Mark
AU  - Midei M
AUID- ORCID: 0000-0003-3192-2668
AD  - Clinical Division Retrotope, Inc. Los Altos California USA.
FAU - Dastgir, Jahannaz
AU  - Dastgir J
AD  - Atlantic Health System Goryeb Children's Hospital Morristown New Jersey USA.
FAU - Flora, Christina
AU  - Flora C
AD  - Atlantic Health System Goryeb Children's Hospital Morristown New Jersey USA.
FAU - Molinari, Robert J
AU  - Molinari RJ
AD  - Clinical Division Retrotope, Inc. Los Altos California USA.
FAU - Heerinckx, Frederic
AU  - Heerinckx F
AD  - Clinical Division Retrotope, Inc. Los Altos California USA.
FAU - Endemann, Sarah
AU  - Endemann S
AD  - Clinical Division Retrotope, Inc. Los Altos California USA.
FAU - Atwal, Paldeep
AU  - Atwal P
AD  - Clinical Division Retrotope, Inc. Los Altos California USA.
FAU - Milner, Peter
AU  - Milner P
AD  - Clinical Division Retrotope, Inc. Los Altos California USA.
FAU - Shchepinov, Mikhail S
AU  - Shchepinov MS
AD  - Clinical Division Retrotope, Inc. Los Altos California USA.
LA  - eng
PT  - Journal Article
DEP - 20200327
PL  - United States
TA  - JIMD Rep
JT  - JIMD reports
JID - 101568557
PMC - PMC7358664
OTO - NOTNLM
OT  - INAD
OT  - NBIA
OT  - PLA2G6
OT  - PLAN
OT  - neurodegeneration
COIS- D. A., J. D., and C. F. declare no conflict of interest. P. M., F. H., M. M., P. 
      A., and M. S., are employed by and holds stock in Retrotope. R. M. is a founder 
      and holds stock in Retrotope, Inc. Sarah Endemann is employed by Retrotope. All 
      authors confirm that the content of the article has not been influenced by the 
      sponsor.
EDAT- 2020/07/21 06:00
MHDA- 2020/07/21 06:01
PMCR- 2020/03/27
CRDT- 2020/07/21 06:00
PHST- 2019/11/11 00:00 [received]
PHST- 2020/03/04 00:00 [revised]
PHST- 2020/03/06 00:00 [accepted]
PHST- 2020/07/21 06:00 [entrez]
PHST- 2020/07/21 06:00 [pubmed]
PHST- 2020/07/21 06:01 [medline]
PHST- 2020/03/27 00:00 [pmc-release]
AID - JMD212116 [pii]
AID - 10.1002/jmd2.12116 [doi]
PST - epublish
SO  - JIMD Rep. 2020 Mar 27;54(1):54-60. doi: 10.1002/jmd2.12116. eCollection 2020 Jul.